Henry Slade and Sam Underhill have been named in England's starting line-up to face Argentina on Saturday as Owen Farrell and Maro Itoje are given a rest.
Centre Slade and flanker Underhill started England's last Test against the Pumas in June and keep their places in the side for the first November international at Twickenham.
British and Irish Lions duo Farrell and Itoje were not included in the matchday squad, with a clash against Australia to come a week later.
Elliot Daly will start on the left wing just a fortnight after suffering a medial knee ligament tear, but Jonny May misses out due to a hamstring injury.
Hooker Jamie George must again settle for a place on the bench, with captain Dylan Hartley retaining his spot.
England head coach Eddie Jones said: "As a squad we have been preparing for this game since our first camp in August and are excited about playing in front of 82,000 fans at Twickenham Stadium on Saturday.
"This is our best 23 selected in what is our most important game this year. We know that Argentina is a strong team - Rugby World Cup semi-finalists in 2015 - and we will have to be smart and play well to beat them."
England: Mike Brown, Anthony Watson, Jonathan Joseph, Henry Slade, Elliot Daly, George Ford, Ben Youngs; Mako Vunipola, Dylan Hartley (captain), Dan Cole, Courtney Lawes, George Kruis, Chris Robshaw, Sam Underhill, Nathan Hughes.
Replacements: Jamie George, Ellis Genge, Harry Williams, Joe Launchbury, Tom Curry, Danny Care, Alex Lozowski, Semesa Rokoduguni.